Dangerous than corticosteroids, used locally and how to safely use them? When they should be applied must, despite the risk of possible adverse effects, and when you can do without them? How can we reduce the harm caused or prevent it altogether from the use of these drugs?
According to international health statistics in the world there is a clear upward trend in the incidence of various allergic diseases [1-2]. Without touching on in this publication are sufficiently important questions the reasons for this (this is the subject of a separate topic), as well as the etiology and prevention of specific diseases, we note that this fact alone makes the development of effective treatments for these conditions is sufficient to date.
Preparations of topical corticosteroids (TC) – in literature, they are sometimes called "locally used" – have traditionally played an important role in the treatment of various skin diseases. Namely cutaneous manifestations are the most common manifestations of various allergic disorders and conditions. And this is due to the very nature of the skin, their function and genetic origin. The main clinical effects of the TC, are known to be anti-inflammatory and immunosuppressive, they provide directly to the skin. In addition, they are highly expressed in fibroblasts inhibit the synthesis of collagen, which plays a key role in the pathogenesis of a number of chronic dermatoses. And then it is worth mentioning the fourth significant therapeutic effect - antipruritic - which is important in the treatment of so-called "itchy dermatosis" treatment of clinical manifestations which dramatically improves the quality of life for sufferers of this disease group of patients.
Penetration of the TC in the systemic circulation outside the scope of causes side effects of these drugs. And by itself this effect in terms of practical application of drugs TC is undesirable. Among the side effects worth mentioning suppression of endogenous production by own corticosteroid, stimulation of blood pressure, etc. All of them in varying degrees can be quite important for the health of the individual patient, causing the appearance or exacerbation of variety complications already have a disease as well as contributing to the emergence of new ones.
The history of the use of corticosteroids topically to the morbid area traces its history to the application of M.Sulzberger and V.Witten in 1952 this method of hydrocortisone [3]. Without exaggeration the appearance of the TC in the clinic has revolutionized approaches to the treatment of a number of dermatological diseases. Subsequent to the modification time of the chemical structure of the TC significantly increased their therapeutic efficacy. But at the same time - and it's worth mentioning separately - has given rise to some new, sometime later to sufficiently undervalued, adverse effects. Sometimes it is very, very important from a medical point of view. Actually it was side effects in a number of clinical cases and a number of diseases in its inevitable appearance and created a halo around these medications especially at risk. It is worth noting that in most cases they are caused by systemic action of drugs is directly related to their resorption into the systemic circulation.
Currently in clinical pharmacology to classify the severity of the TC by the vasoconstrictive effect on the 4 types (Table 1). This effect was recorded in experiments on rabbit ear vessels. Adopted by the division is largely consistent with their clinical efficacy ("strength of action"). But at the same time, the clinical efficacy of this group of drugs, as well - which is important in itself - the possible side effects also depend on:
• chemical type of TC and its dosage form;
• frequency, duration and method of use of the drug in each case;
• type of pathology of the skin, as well as the area most of its destruction;
• other relevant factors - age and patient's comorbidities, the localization of disease on the body, etc.
To obtain the maximum therapeutic effect with the least possible adverse events must necessarily take into account all these factors [4-5]. What in practice does not always.
Characteristics of the various dosage forms of topical corticosteroids. To assist local pharmacological effect of the TC should get used dosage form in the epidermis and dermis. The rate of this penetration depends on your dosage form (ointment, cream, lotion), and on the lipophilicity (affinity to dissolve in fat) molecules of the corticosteroid. The more lipophilic it is, the greater the concentration of the drug accumulates in the cells of the skin and the slower one goes into the bloodstream, providing a variety of side effects.
TC among one group, and in most cases and compared with other dosage forms of the same steroid ointment based on it have greater therapeutic potential because of local obstructive effect (similar to a bandage, do not let the water). At the same time significantly increases the penetration of drug into the skin. In medical practice the ointment is most often used for dry, wrinkled, cracked and lichenificated skin. Foremost because of dampening effect of the dosage form.
Unlike creams, ointments (representing oil suspensions and emulsions in water) locally exhibit a well-known to all dermatologists drying effect. And because they are more suitable for acute and subacute so-called "weeping" skin lesions (manifested in the separation of the liquid surface damage - the lymph, inflammatory exudate, etc.). In this case, because of the local vasoconstrictor effect of corticosteroids, this effect is enhanced. That is referred to the influence of the drug reduces the formation of fluid in the skin. This dosage form is most suitable for the treatment of the nature of the wet areas of the skin (e.g., lips, axilla, perineum, etc.), large skin folds (folds under the breast, enlarged abdomen), and periarthric bends (elbows bend, popliteal fosse, etc.). At the same time, assigning or using a specific TC, please note that the creams in their production require the inclusion of the various excipients (emulsifiers, stabilizers, etc.), most of which have the allergic potential and often do cause different side effects. In this regard, it is quite critical to treat the appearance / change of allergic symptoms in the first few days after using the cream. And if there is suspicion and the more objective evidence in favor of a possible allergic reaction to medication it must be abolish immediately.
For scalp TC are often used as a lotion or gel. These dosage forms there are a definite lack of moisturizing effect, what they actually are similar to creams and ointments. In some formulations introduces the basis of propylene glycol, which enhances the penetration of the drug. Thus, changing the basis of TC expected therapeutic effect can be increased substantially [6]. But in practice, in order to obtain the maximum therapeutic effect and fast with the minimum possible adverse reactions should be above all things to consider.
Features of a variety of topical corticosteroids. Acute inflammatory diseases of the skin (such as atopic dermatitis and eczema, acute contact dermatitis, etc.) are an indication for the use of TC low activity and active (respectively, Groups I and II in Table 1). Chronic or dermatoses with hyperkeratosis usually treated groups in the active and highly active drugs (Groups III and IV). Table 2 shows the degree of effectiveness of TC for various skin diseases. Less amenable to such treatment of the disease are more likely to require in each case, the drug the next highest group.
As a rule, all TC, if a doctor is assigned to another, using a stereotyped - a small amount of ointment (cream) – 1-2 cm extruded from the tube – is applied gently rubbing the affected surface of the skin 1-2 times per day. Continuous course of treatment in most cases should not exceed two weeks.
Table 1. Corticosteroids for topical use
Each group of drugs has its more refined indications. For example, hydrocortisone cream (1%) is indicated for the short treatment of children and infants, and adults with subacute and effaced forms of skin inflammation. At the same time with worsening of skin diseases require more potent drugs. In this case, preferably the new non-halogenated TC. One of the most well-proven in a clinical setting – methylprednisolone aceponat (Advantan), which for once daily use is close to the effectiveness of halogenated drugs (betamethasone valerate) twice during their daily use. The lack of ability in Advantan affect the level of the endogenous circadian rhythm of glucocorticoids is an important property for pediatric dermatology, because children are generally more sensitive to side effects of the CS [6, 7].
Efficacy or potency of the TC can be increased by the use of "under the bandage. In this method significantly increases skin hydration and increased penetration of the active substance in it. However, you should always remember, at the same time increases the risk of various adverse effects, especially if you use this method for a long time. For this purpose, can be used polyethylene gloves, plastic films and a variety of bio-occlusive covering (e.g. hydrocolloids).
Table. 2. The effectiveness of topical corticosteroids for various skin diseases
Features of application of topical corticosteroids in various areas of the skin. The thickness of the epidermis and whole skin, various local factors - such as temperature and humidity of a certain area of the skin - are factors that can significantly affect the degree of penetration and the subsequent effect of the drug. And similarly affect the risk of possible adverse effects of treatment.
In descending order of penetration – this mucosa, scrotum, the folds under the breasts, axillary and perineal folds, eyelids, face, chest and back, arms and legs, shins and forearms, the back surfaces of the hands and feet, hands and back of hands and skin fingernails. Typically the first group of TC is preferable for use on the face and in the natural folds (ulnar, axillary, groin, etc.). If in connection with a specific disease requires the use of more efficient TC, in these areas it is only recommended for short-term use (1-2 weeks). On the other hand, palms and soles, with a fairly thick and solid structure of the skin initially require the use of TC group III or IV. It is also necessary because there are frequent accidental deletion is superimposed layers of the drug. In some cases, justified by the alternate use of two or more different drugs of this type. Various TC can be used simultaneously when it comes to applying them to different regions of the body structure and, consequently, of the skin.
Other factors. In children, especially infants, there is a natural increase in the ratio of body surface to their weight. In addition premature infants and young children the elderly are relatively thin skin that in all these cases causes an increase in the degree of system penetration of the TC. In these patient groups is preferable to use of corticosteroids low level activity.
If the treatment being relatively large part of the body in all cases preferable to the use of TC with low and medium activity due to increased risk of side effects
Given the common practice of delusion, we must remember that:
1. Treatment of TC must stop immediately on the disappearance of symptoms of skin disease. This group of drugs in any case not is used to prevent its occurrence.
2. If it is permissible and possible, the intermittent use of an ointment or cream is preferable to continuous and prolonged use. This method prevents the development of tachyphylaxis and significantly reduces the risk of adverse effects of treatment.
3. We must remember that these drugs are not used for the treatment of acne and its complications. They are not used for skin lesions with signs of infection.
4. Long-term use of TC is particularly desirable to avoid the face and sensitive areas of skin.
5. It should be borne in mind that some patients and certain forms of skin diseases currents respond better to use TC more potent in the early treatment group. Moreover according to doctor's prescriptions he then replaced them on a less powerful, the conventional application conditions.
Side-effects. Available to date clinical data suggest that the higher the TC, in particular the local medical activity, the greater the risk for a variety of adverse effects. However they also occur more rapidly in time from the start using the drug. All of these effects, which must be remembered, can be divided into three groups (Table 3). The first is the adverse effects caused by the TC and depend on its pharmacological properties. The second group are presented allergic response to the ingredients of the dosage form. And separately the third group represented by the adverse effects caused by long periods of use of this type drugs.
Table. 3. Adverse effects associated with topical corticosteroids
Group 1 Atrophy of the skin and subcutaneous tissue Skin striae, atrophic strips Steroid purpura and bleeding Telangiectasia Hypo-or hyperpigmentation of the skin Periocular, perioral dermatitis Folliculitis Acne rash Hypertrichosis or alopecia Secondary infection and exacerbation of bacterial infections Masking and generalization of fungal infection Detained wound healing Cataracts or glaucoma Group 2 Contact dermatitis - ingredients and excipients - corticosteroid directly Group 3 With prolonged use in large areas of the body increases the risk - edemata - hypertension - hyperglycaemia - symptoms of Cushing - decrease in resistance of the organism |
It should be noted that systemic side effects when using the TC occur as an extreme exception. Risk groups for them are young children as well as people that use drugs for a long time and over large areas of skin. As a rule this is a question of self-medication uncontrolled and its consequences. Such actions may in some cases provoke adrenal suppression, growth retardation, development of cushingoid syndrome and hypertension. The literature reported cases of cataracts and glaucoma with prolonged and uncontrolled use of topical corticosteroids in uveitis.
In all cases, the occurrence of adverse reactions or signs of infection in the use of topical corticosteroid use of the drug must be stopped immediately!
Conclusions. Topical corticosteroids, if properly selected by their action and dosage form, play an important positive role in the effective treatment of various skin diseases. At the same time it must be remembered though that risk is relatively small, about the likely adverse effects, such as various forms of atrophy and dispigmentation of skin.
References
1. Bachot N., Roujeau J.C. Differential diagnosis of severe cutaneous drug eruptions // Am J Clin Dermatol 2003; 4: 561-572.
2. Drake LA, Dinehart SM, Farmer ER et al. Guidelines of care for the use of topical glucocorticosteroids. American Academy of Dermatology // J Am Acad Dermatol 1996;35:615-9.
3. Sulzberger M.B., Witten
4. Giannotti B., Haneke E. Eczema. England 1995;74.
5. Griffiths WA Oxford
6. Компендиум 2005 - лекарственные препараты / Под ред. В.Н.Коваленко, А.П.Викторова. – К.: Морион, 2005. – 1920 с.
6. Компендиум 2005 - лекарственные препараты / Под ред. В.Н.Коваленко, А.П.Викторова. – К.: Морион, 2005. – 1920 с.
7. Stoughton New York
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